1. Field of the Invention
This invention relates to compounds substituted with a tetrahydro-2H,4H-1,3,6-dioxazocino (i.e., with an N-1,3,6-dioxazocanyl moiety) and to the preparation thereof.
2. Description of the Prior Art
Copending U.S. patent application Ser. No. (836,010) of Stanley M. Bloom, Alan L. Borror and James W. Foley filed concurrently herewith is directed to a method of synthesizing 3,3-disubstituted-2,3-dihydrobenz[d]isothiazole-1,1-dioxides possessing a carbonyl group in the 2-position. Depending upon the carbonyl group and the 3,3 substituents, the products of the synthesis may be employed as pH-sensitive indicator dyes, antihalo dyes or photographic optical filter agents. As disclosed and claimed therein, the method of preparing these compounds comprises reacting a 3-(4'-OP-1'-phenyl/4'-OP-1'-naphthyl)-3-(phenyl/naphthyl)-2,3-dihydrobenz[ d]-isothiazole-1,1-dioxide wherein P is a protecting group compatible with organometallic reagents and a carboxylic acid halide in the presence of pyridine to yield the corresponding 2-carbonyl derivative. Optionally, the acylation may be carried out by sequentially reacting the said isothiazole compound with an alkali metal hydride to give the corresponding 2-alkali metal salt followed by reaction with the selected carboxylic acid halide. The acylated compound thus prepared is then treated with acid to remove the protecting group and yield the product.
The 3-(4'-OP-1'-phenyl/4'-OP-1'-naphthyl)-3-(phenyl/naphthyl)-2,3-dihydrobenz[ d]isothiazole-1,1-dioxides employed as intermediates in the above method may be synthesized by reacting a 3-(4'-OP-1'-phenyl/4'-OP-1'-naphthyl)benz[d]isothiazole 1,1-dioxide and a phenyllithium or a naphthyllithium reagent as disclosed and claimed in copending U.S. patent application Ser. No. 836,008 of Alan L. Borror, Louis Cincotta, James W. Foley and Marcis M. Kampe filed concurrently herewith. The 3-(4'-OP-1'-phenyl/4'-OP-1'-naphthyl)benz[d]isothiazole-1,1-dioxides, which form the subject matter of copending U.S. patent application Ser. No. 836,024 of Alan L. Borror, Louis Cincotta, Ernest W. Ellis, James W. Foley and Marcis M. Kampe filed concurrently herewith, are prepared by converting a blocked 4-halophenol or a blocked 4-halo-1-naphthol to the corresponding Grignard or lithium reagent and then reacting this reagent with saccharin, a saccharin salt or saccharin psuedo-chloride.
As discussed in the aforementioned applications, protecting groups, such as, methoxymethyl and 2-tetrahydropyranyl are useful in preparing the blocked phenols and blocked 1-naphthols, and in addition to protecting the functional hydroxy group, are useful for protecting other hydroxy groups that may be present. For example, such groups may be used to protect an --N(CH.sub.2 CH.sub.2 OH).sub.2 substituent.
In compounds, such as, HO(CH.sub.2).sub.2 OH and HO(CH.sub.2).sub.3 OH, other means for protecting the hydroxy groups also have been employed. In one such method, the 1,2- or 1,3-alkanediol is reacted with formaldehyde in the presence of acid to give the corresponding ring-closed compound, ##STR1## However, attempts to ring-close an --N,N-di(.beta.-hydroxyethyl) moiety employing this rection have been unsuccessful.
E. V. Dehmlow and J. Schmidt, Tetrahedron Lett., No. 2, p. 95 (1976) have reported that dichloromethane reacts with alkylOH and arylOH in the presence of solid potassium hydroxide and a quaternary ammonium salt to form the corresponding di(alkoxy)methanes and di(aryloxy)methanes as illustrated below. EQU 2alkylOH+CH.sub.2 Cl.sub.2 .fwdarw.alkyl--O--CH.sub.2 --O--alkyl EQU 2arylOH+CH.sub.2 Cl.sub.2 .fwdarw.aryl--O--CH.sub.2 --O--aryl
Quite unexpectedly, it has been found that this reaction can be applied to an --N,N-di(.beta.-hydroxyethyl) moiety to yield a cyclic product rather than a polymeric product.
In one aspect, the present invention is concerned with the reaction of a dihalomethane and compounds possessing an --N,N-di(.beta.-hydroxyethyl) substituent to protect the hydroxy groups by the formation of a cyclic moiety compatible with and stable in the presence of organometallic reagents. In another aspect, the present invention is concerned with the ring-closed products thus formed.